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CURRENT RESEARCH PROJECTS

My laboratory has pioneered research into the role of the tumour microenvironment for improved anti-cancer immunotherapies with a specific focus on tumour vessel remodelling. To reach tumour cells within a cancer, immune cells must enter the tumour blood vessels, cross the vessel wall, and find their way through tumour stroma. We have shown that tortuous tumour blood vessels are a critical barrier that limits anti-cancer therapy at the tumour site. In contrast, ‘normalization’ of tumour blood vessels, the transformation of aberrant tumour vessels into a more functional or “normal” vasculature, enhances immune cell infiltration and anti-tumour immunity.

Figure 1: Blood vessels in healthy and cancerous tissue. Source: Ruth Ganss

Project

Stromal precision targeting using cytokine-peptide delivery systems

Project

Stromal precision targeting using cytokine-peptide delivery systems

Project Outline

We have developed new tools which target abnormal tumour stromal features to increase homing and/or priming of cytotoxic T cells at the tumour site.
This includes normalization and decompression of tumour blood vessels to increase cancer perfusion, and the transformation of tumour endothelial cells into so called “High Endothelial Venules” (HEVs). HEVs are entrance portals for lymphocytes and associated with ectopic intratumoral lymph nodes which facilitate T cell priming (Figure 2). We are now seeking to expand these technologies, in particular induction of intratumoral lymph nodes, to advanced and hard-to-treat cancers where current immunotherapies fail.

Figure 2: Tumour (blue) with therapeutically induced HEVs and lymph node structure (red).  Source: Anna Johansson-Percival

Research area
Cancer

Laboratory
Cancer microenvironment

Contact
Professor Ruth Ganss
[email protected]

Project

Drug-repurposing for stromal remodelling

Project

Drug-repurposing for stromal remodelling

Project Outline

Drugs that produce sustained normalization effects in cancer are limited
We recently discovered the role of pericyte (cells which wrap around and support endothelial cells) differentiation in the processes of tumour blood vessel normalization, tumour perfusion and penetration of anti-tumour immune effector cells. We are now aiming to elucidate mechanisms of pericyte plasticity in cancer.  In this project, we are using genetically modified mouse models to identify key factors that improve vessel patency, and, importantly, drugs which mimic therapeutic effects observed in genetic models.

Research area
Cancer

Laboratory
Cancer Microenvironment

Contact
Professor Ruth Ganss
[email protected]

CURRENT STUDENT PROJECTS

Student Project

Analysing the “Blood-Tumour” Barrier

Student Project

Analysing the “Blood-Tumour” Barrier

Project Outline

To reach tumour cells within malignant tissue, immune cells and drugs must enter the tumour blood vessels, cross the vessel wall, and penetrate through tumour stroma.
We have previously shown that chaotic blood vessels and lack of tumour perfusion are critical barriers that limit anti-cancer therapy at the tumour site. These intratumoral parameters are in large part a manifestation of the tumour stroma which includes the newly formed, angiogenic vasculature. Our laboratory seeks to understand molecular mechanisms of stromal remodelling in tumours with the goal to develop improved therapies by modifying the tumour microenvironment.

Specifically, we are studying mouse models of cancer to develop new approaches which exploit the dynamic nature of tumour stroma to reprogram rather than destroy vessels which provides longer lasting antitumor effects, in particular when combined with immune strategies to eliminate cancer cells. In the course of this project fundamental changes in the tumour vascular bed and stroma before and after therapy will be analysed by histology, quantitative PCR and Western Blots. Vascular cells with overexpression or deletion of specific genes will be employed to assess cytoskeletal rearrangements, migration and signalling events. This project aims to identify molecular mechanisms and signalling pathways which define tumour stroma which is permissive for destruction.

Chief supervisor
Professor Ruth Ganss

Project suitable for
PhD

Essential qualifications
BSc Hons